Urea stabilized epinephrine mist for treatment of asthma



Patented Apr. 11,1950

S PATENT OFFICE UREA STABILIZED EPINEPHRINE MIST FOR TREATMENT OF ASTHMA Harold Alexander Abramson, New York, N. Y.

N Drawing. Application June 5, 1946, Serial No. 674,635

2 Claims. (Cl. 16758) My present invention relates, generally, to therapeutic compositions useful in the treatment of asthma, and it has particular relation to such compositions adapted for the nebulization therapy of asthma.

This invention is a continuation-in-part of my copending application, Serial No. 411,987, filed September 23, 1941, for Solutions for the improved nebulization therapy of the lungs and bronchioles, which issued as Patent No. 2,414,918 on January 28, 1947.

The use of vasoconstrictive or antispasmodic substances in the treatment of asthma, is well known. In order to provide complete treatment and relief of asthmatic attacks, it is necessary to have the therapeutic compositions reach the bronchioles and recesses of the lungs in an effective state so that vasoconstrictive action may be obtained.

The primary object of this invention is the provision of an improved therapeutic composition which, upon nebulization, forms a mist or aerosol of such stability that it may be inhaled into the bronchioles and lung recesses.

Another object of the invention is the provision of improved therapeutic compositions adapted for the nebulization therapy of asthma, which allow the patient to readily estimate the dosage of the composition being used.

Other objects of the invention will, in part, be obvious and will in part appear hereinafter.

For a more complete understanding of the nature and scope of the invention, reference may be had to the following detail description thereof wherein preferred formulations are set forth, and modifications and substitutions are suggested.

In treating asthmatic patients with available therapeutic compositions containing vasoconstrictive and antispasmodic substances, by the nebulization technic, it became evident that complete treatment and 'full relief were not being afforded. According to standard practice, patients were directed to inhale the discharge from a nebulizer containing a conventional aqueous solution of a vasoconstrictive or antispasmodic substance, such as 1% of an epinephrine salt. These conventional solutions might contain additional ingredients such as germicidal agents and preservatives, but were generally isotonic or only slightly hypertonic. After considerable experience in treating asthmatic patients with such compositions and according to standard nebulization technic, the conclusion was reached that such compositions and the treatment therewith, were only partially effective.

A further disadvantage of the conventional therapeutic compositions provided for the nebulization therapy of asthma, was the inability of the patient to ascertain whether or not he was obtaining a mist of the composition for inhalation. Since, such mists as were formed with the conventional compositions, disappeared rapidly, the patient could neither see them nor judge the dosage with any degree of accuracy. Therefore, the technic was psychologicall disadvantageous and many patients would discontinue the use of such conventional aqueous solutions of vasoconstrictive substances.

According to my invention, it was found that by dissolving at least certain minimum amounts of a number of solutes in the aqueous solutions of vasoconstrictive and antispasmodic substances, stable mists or aerosol clouds of the compositions would be formed upon nebulization. The most important characteristic of these mists and aerosol clouds is that they have such a degree of stability as to permit them to be inhaled and carried by the respiratory movement into the furthest recesses of the lungs where the therapeutic substance thus transported, can act upon the bronchioles and other tissues which are responsible for the asthmatic attacks. With less stable mists, the beneficial effects of the vasoconstrictive substances were largely restricted to the nasal and oral areas.

Accordingly, I provide therapeutic compositions adapted for the treatment of asthma, which, in addition to the conventional formulations having a minor amount of a vasoconstrictive or antispasmodic substance dissolved in an aqueous solution, have included at least a predetermined minimum amount of urea which serves to sta- 'bilize the mist formed upon nebulization of the composition.

In my copending application, Serial No. 411,987, filed September 23, 1941, of which the present application is a continuation-in-part, I have disclosed a number of solutes which are non-toxic and which serve to stabilize the mist formed upon nebulization, when included in certain minimum amounts. The non-toxic solutes disclosed in said application Serial No. 411,987, are selected from the group consisting of non-toxic salts, polyhydric alcohols, sugars, and urea.

The present application is specifically directed to the use of urea as the non-toxic solute, and

to the improved therapeutic compositions incorporating the same.

The following are examples of antispasmodic or vasoconstrictive substances which may be used in minor amounts in therapeutic compositions provided in accordance with my invention: epinephrine (adrenaline), amphetamine, ephedrine, neosynephrine and benzedrine. These substances are ordinarily used in the form of their salts, such as the phosphate, hydrochloride or sulphite. They are used in minor amounts, such as from about 0.5% to 2% by weight of the aqueous solution.

Although there is probably no chemical combination of the stabilizing solutes employed in accordance with my invention, with the vasoconstrictive substances, and the stabilizing relationship is probably due to physical relationships, I have found that epinephrine is the preferred vasoconstrictive and antispasmodic substance for the combination. The hydrochloride or phosphate salts of epinephrine are usually employed.

It will be understood that a combination of vasoconstrictors and antispasmodics may be used. A preferred combination is epinephrine and neosynephrine.

As stated above, this present invention is particularly directed to the use of urea as the mist stabilizing solute. Although an addition of urea amounting to at least 5% by weight of the aqueous solution is adequate, I prefer to employ at least 7.5%. Urea serves not only as a mist stabilizing solute in my therapeutic compositions, but also has remarkable bacterio-static properties and thereby serves a dual function.

The upper limit onthe concentration of urea is not critical and will depend upon the limit. at which objectionable irritations would be experienced by the patient. However, it may be used in concentrations considerably in excess of 5%, the minimum effective concentration.

The following specific formulations are given as illustrative of preferred embodiments of the Water to 100 cc.

Water to cc.

It will be understood that in addition to the foregoing specific examples, other formulations inay be provided which also embody the invenion.

Having fully described the invention, what I claim as new is:

l. A therapeutic composition adapted for the nebulization therapy of asthma which comprises an aqueous solution containing about 1.0% by weight of an epinephrine salt, and at least 7.5% by weight of urea which serves to stabilize the mist formed on nebulization of said therapeutic composition.

2. A therapeutic composition adapted for the nebulization therapy of asthma which comprises an aqueous solution containing from about 0.5% to about 2% by Weight of an epinephrine salt, and. at least 7.5% by weight of urea which serves to stabilize the mist formed on nebulization of said therapeutic composition, the balance of the composition being substantially entirely water.

HAROLD ALEXANDER ABRAMSON.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,103,160 Kircher et al Dec. 21, 1937 2,415,719 Abramson Feb. 11, 1947 OTHER REFERENCES Drug and Cosmetic Industry, Oct. 1943, page 433.

Robinson American Journal of Surgery, vol. 35, No. 2, 1936, pages 192-197. 

2. A THERAPEUTIC COMPOSITION ADAPTED FOR THE NEBULIZATION THERAPY OF ASTHMA WHICH COMPRISES AN AQUEOUS SOLUTION CONTAINING FROM ABOUT 0.5% TO ABOUT 2% BY WEIGHT OF AN EPINEPHRINE SALT, AND AT LEAST 7.5% BY WEIGHT OF UREA WHICH SERVES TO STABILIZE THE MIST FORMED ON NEBULIZATION OF SAID THEREAPEUTIC COMPOSITION, THE BALANCE OF THE COMPOSITION BEING SUBSTANTIALLY ENTIRELY WATER. 